A multicenter, prospective, randomized, open-label, controlled trial to evaluate the efficacy and safety of zanubrutinib, rituximab and lenalidomide (ZR2) versus rituximab combined with low-dose CHOP (R-miniCHOP) in the treatment of unfit or frail de novo diffuse large B-cell lymphoma patients aged older than or equal to 70 years
This study will evaluate the efficacy and safety of ZR2 versus R-miniCHOP in the treatment of unfit or frail de novo diffuse large B-cell lymphoma patients aged older than or equal to 70 years. Subjects will be randomly assigned 1:1 to ZR2 or R-miniCHOP regimen. The stratification will be performed according to international prognostic index (0-2 / 3-5). Patients in ZR2 group will receive 6 cycles of zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days. Patients in R-miniCHOP group will receive rituximab 375 mg/m² on day 1, cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and vincristine 1 mg on day 2, and prednisone 40 mg/m² on days 2-6, every 21 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
280
Patients in ZR2 group will receive 6 cycles of zanubrutinib 160mg bid, day 1-21, orally, lenalidomide 25mg qd, day 2-11, orally, rituximab 375mg/m², day 1, intravenously, every 21 days.
Patients in R-miniCHOP group will receive rituximab 375 mg/m² on day 1, cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and vincristine 1 mg on day 2, and prednisone 40 mg/m² on days 2-6, every 21 days.
Ruijin Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGProgression free survival
Progression-free survival was defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
Time frame: Baseline up to data cut-off (up to approximately 2 years)
Complete response rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Overall survival
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Time frame: Baseline up to data cut-off (up to approximately 2 years)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: From enrollment to study completion, a maximum of 4 years
Percentage of Participants Achieving Meaningful Improvement in European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)
Quality of Life will be assessed by EORTC QLQ-C30 (Verison 3.0).
Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
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Percentage of Participants Achieving Meaningful Improvement in EORTC QLQ-ELD14 (Elderly Module)
Quality of Life will be assessed by EORTC QLQ-ELD14.
Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion
Percentage of Participants Achieving Meaningful Improvement in Functional Assessment of Cancer Therapy-Lymphoma Lymphoma Subscale (FACT-Lym LymS)
Quality of Life will be assessed by FACT-Lym LymS.
Time frame: Day 1 of Cycles 1 and 4 (Cycle length=21 days); 30 days after treatment completion